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Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and growth by matrix metalloproteinase-dependent and independent mechanisms

, : Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and growth by matrix metalloproteinase-dependent and independent mechanisms. Breast Cancer Research 11(2): R24-R24

The stromal microenvironment has a profound influence on tumour cell behaviour. In tumours, the extracellular matrix (ECM) composition differs from normal tissue and allows novel interactions to influence tumour cell function. The ECM protein tenascin-C (TNC) is frequently up-regulated in breast cancer and we have previously identified two novel isoforms - one containing exon 16 (TNC-16) and one containing exons 14 plus 16 (TNC-14/16). The present study has analysed the functional significance of this altered TNC isoform profile in breast cancer. TNC-16 and TNC-14/16 splice variants were generated using PCR-ligation and over-expressed in breast cancer cells (MCF-7, T47D, MDA-MD-231, MDA-MB-468, GI101) and human fibroblasts. The effects of these variants on tumour cell invasion and proliferation were measured and compared with the effects of the large (TNC-L) and fully spliced small (TNC-S) isoforms. TNC-16 and TNC-14/16 significantly enhanced tumour cell proliferation (P < 0.05) and invasion, both directly (P < 0.01) and as a response to transfected fibroblast expression (P < 0.05) with this effect being dependent on tumour cell interaction with TNC, because TNC-blocking antibodies abrogated these responses. An analysis of 19 matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases 1 to 4 (TIMP 1 to 4) revealed that TNC up-regulated expression of MMP-13 and TIMP-3 two to four fold relative to vector, and invasion was reduced in the presence of MMP inhibitor GM6001. However, this effect was not isoform-specific but was elicited equally by all TNC isoforms. These results demonstrate a dual requirement for TNC and MMP in enhancing breast cancer cell invasion, and identify a significant role for the tumour-associated TNC-16 and TNC-14/16 in promoting tumour invasion, although these isoform-specific effects appear to be mediated through MMP-independent mechanisms.


PMID: 19405959

DOI: 10.1186/bcr2251

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Bjorkman, L.; Feurdean, A.; Wohlfarth, B., 2003: Late-Glacial and Holocene forest dynamics at Steregoiu in the Gutaiului Mountains, Northwest Romania. Pollen analyses and AMS 14C measurements were performed on lacustrine sediments and peat deposits from the former crater lake Steregoiu in a mid-altitude area in the Gutaiului Mountains in NW Romania in order to provide a detailed reconstruction o...

Lund, P.A.; Large, A.T.; Kapatai, G., 2003: The chaperonins: perspectives from the Archaea. Heat-shock protein (Hsp) 60 chaperones are almost ubiquitous and almost always essential. They can be divided on the basis of sequence homology into two broad types: group I (found in bacteria, mitochondria and chloroplasts) and group II (found in...

Mengel, H., 1965: Comparative studies on the effect of normal and dry diet on body weight and serological reactivity of guinea pigs. A dried feed for guinea pigs favored weight gain, higher serum C'-titers (during 1st 3 wk. feeding only) and less weight loss following vein-puncture or immunization stresses, as compared with conventional guinea pig feed.

Cabrera-Ponce, J.; Vegas-Garcia, A.H.rrera-Estrella, L., 1995: Herbicide resistant transgenic papaya plants produced by an efficient particle bombardment transformant method. A system for the production of transgenic papaya (Carica papaya L.) plants using zygotic embryos and embryogenic callus as target cells for particle bombardment is described. Phosphinothricin (bar) and kanamycin (npt II) resistance genes were used...

Wang, L.; Zhang, G.H.; Wang, X.Q.; Zhu, L.Y.; Xu, D., 2016: Guanidine-phosphate non-covalent interaction in LAP crystal growth solution evidenced from spectroscopy studies. The similar L-arginine molecule aggregation has been found in L-arginine (LA) and L-arginine phosphate monohydrate (LAP) aqueous solutions. The special fluorescence emission at 380 nm of LA aggregates in LAP solution has been found, compared with...

Kreyberg, L., 1973: Reminiscences from the Norwegian Pathology Society. Tidsskrift for den Norske Laegeforening 93(31): 2285-2289

Ikeda, N., 2012: The discoveries of uranium 237 and symmetric fission - from the archival papers of Nishina and Kimura. Shortly before the Second World War time, Nishina reported on a series of prominent nuclear physical and radiochemical studies in collaboration with Kimura. They artificially produced (231)Th, a member of the natural actinium series of nuclides, b...

Rullier, A.;, B.; Urbaniak, R.; Ghetti, S.; Carles, J.; Balabaud, C.; Bianchi, F.B.; Ballardini, G.; Bioulac Sage, P., 1998: Immunohistochemical detection of HCV in 52 liver cirrhosis with or without hepatocellular carcinomas. Hepatology 28(4 PART 2): 563A, Oct

Amadon, D., 1964: A new hall of North American birds. Curator, 7: 171-179

Larrondo, J.; Porte, L.; Gosch, M.; Cabrera, R.; Weitzel, T., 2016: Trichobacteriosis axillaris caused by Dermabacter hominis. Journal of the European Academy of Dermatology and Venereology 31(5): E267-E268